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Long-term impact of maternal obesity on the gliovascular unit and ephrin signaling in the hippocampus of adult offspring.
Shiadeh, Seyedeh Marziyeh Jabbari; Goretta, Fanny; Svedin, Pernilla; Jansson, Thomas; Mallard, Carina; Ardalan, Maryam.
Affiliation
  • Shiadeh SMJ; Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Goretta F; Department of Clinical Medicine, Translational Neuropsychiatry Unit, Aarhus University, Aarhus, Denmark.
  • Svedin P; Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Jansson T; Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Mallard C; Division of Reproductive Sciences, Department of OB/GYN, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
  • Ardalan M; Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
J Neuroinflammation ; 21(1): 39, 2024 Feb 02.
Article in En | MEDLINE | ID: mdl-38308309
ABSTRACT

BACKGROUND:

Children born to obese mothers are at increased risk of developing mood disorders and cognitive impairment. Experimental studies have reported structural changes in the brain such as the gliovascular unit as well as activation of neuroinflammatory cells as a part of neuroinflammation processing in aged offspring of obese mothers. However, the molecular mechanisms linking maternal obesity to poor neurodevelopmental outcomes are not well established. The ephrin system plays a major role in a variety of cellular processes including cell-cell interaction, synaptic plasticity, and long-term potentiation. Therefore, in this study we determined the impact of maternal obesity in pregnancy on cortical, hippocampal development, vasculature and ephrin-A3/EphA4-signaling, in the adult offspring in mice.

METHODS:

Maternal obesity was induced in mice by a high fat/high sugar Western type of diet (HF/HS). We collected brain tissue (prefrontal cortex and hippocampus) from 6-month-old offspring of obese and lean (control) dams. Hippocampal volume, cortical thickness, myelination of white matter, density of astrocytes and microglia in relation to their activity were analyzed using 3-D stereological quantification. mRNA expression of ephrin-A3, EphA4 and synaptic markers were measured by qPCR in the brain tissue. Moreover, expression of gap junction protein connexin-43, lipocalin-2, and vascular CD31/Aquaporin 4 were determined in the hippocampus by immunohistochemistry.

RESULTS:

Volume of hippocampus and cortical thickness were significantly smaller, and myelination impaired, while mRNA levels of hippocampal EphA4 and post-synaptic density (PSD) 95 were significantly lower in the hippocampus in the offspring of obese dams as compared to offspring of controls. Further analysis of the hippocampal gliovascular unit indicated higher coverage of capillaries by astrocytic end-feet, expression of connexin-43 and lipocalin-2 in endothelial cells in the offspring of obese dams. In addition, offspring of obese dams demonstrated activation of microglia together with higher density of cells, while astrocyte cell density was lower.

CONCLUSION:

Maternal obesity affects brain size, impairs myelination, disrupts the hippocampal gliovascular unit and decreases the mRNA expression of EphA4 and PSD-95 in the hippocampus of adult offspring. These results indicate that the vasculature-glia cross-talk may be an important mediator of altered synaptic plasticity, which could be a link between maternal obesity and neurodevelopmental/neuropsychiatric disorders in the offspring.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Prenatal Exposure Delayed Effects / Obesity, Maternal Limits: Aged / Animals / Child / Female / Humans / Infant / Pregnancy Language: En Journal: J Neuroinflammation Journal subject: NEUROLOGIA Year: 2024 Document type: Article Affiliation country: Sweden Country of publication: United kingdom

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Prenatal Exposure Delayed Effects / Obesity, Maternal Limits: Aged / Animals / Child / Female / Humans / Infant / Pregnancy Language: En Journal: J Neuroinflammation Journal subject: NEUROLOGIA Year: 2024 Document type: Article Affiliation country: Sweden Country of publication: United kingdom